Brain Metals Atlas

Towards an Open Multi-Scale Atlas of Metals in the Human Brain

The development of the human brain atlas of metals will offer researchers simple and open access to information on new metal-based perspectives of the human brain and its function. The collection aims to capture (i) multiples scales, (i) multiples metals and (i) multiples conditions.

Introduction to the Atlas

Metals are an integral part of the human brain, contributing to the basic architecture as well as the dynamic function and plasticity of neural systems across scales.

To date, there has yet to be a comprehensive, online, open, atlas of the distribution and function of metals in the human brain. We have thus begun construction of such a digital repository for imaging and other techniques that provides information on the distribution and functional significance of metals in the typical brain and conditions such as epilepsy and Williams syndrome (WS).

Mapping Across Scales

At what scale or resolution are you imaging?

We are using two forms of X-ray fluorescence (XRF) imaging at the Stanford Synchrotron Radiation Lightsource (SSRL). The rapid-scanning X-ray fluorescence imaging (on beamline 10-2) enables both rapid spatial mapping and fine detail of small areas. The following example shows the distributions of zinc in a sagittal section of WS cerebellum. In this example scans were performed at resolutions of (A) 100µm, (B) 40µm, and (C) 10µm.

Although rapid scan resolution is insufficient to examine distribution at the cellular level, the addition of microprobe scanning (BL 2-3) allows us to scan at resolutions of 1 µm (cellular level) in areas of particular interest. Below is the distribution of iron (red) and zinc (blue) in a 100µm section of control tissue with resolution at 5µm:

Metal Colocalization

What’s the big deal with XRF? How is it different from traditional histological techniques?

Rapid scan X-ray fluorescence imaging provides a non-destructive method to contrast and compare between and within brain structures using biologically relevant metals as markers. The technique allows for coregistering distribution of different metals in human brain tissue that are otherwise challenging to examine given common fixation methods (Occipital coronal section, typical developing).

Mapping Brain Structures & Pathways

What structures are you studying?

XRF images are being acquired for a range of brain structures. Rapid scan images showed differential levels of iron and zinc in axonal tracts and grey matter of cortical and subcortical areas.

Across Conditions

What conditions are you studying?

Data in the repository already include examples from across a range of scales and conditions such as typical developing, Williams syndrome and temporal lobe epilepsy.

Acknowledgments

The atlas is being built and maintained by the Green Neuroscience Laboratory, Neurolinx Research Institute. Major portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL). Tissue for this research was obtained from the Salk Williams Syndrome Brain Repository directed by Ursula Bellugi and the Carlen laboratory at the Toronto Western Research Institute. Tissue preparation and analysis was made possible with the help of Terry Sejnowski at the Computational Neurobiology Laboratory, Laura Frutos at the Green Neuroscience Laboratory and researchers at the University of Toronto including Carlos M. Florez, Shanthi Mylvaganam, Taufik Valiante and Peter L. Carlen. Our research was also was supported by UCSD’s Institute for Neural Computation (INC) and the NIH. We greatly appreciate the support of all the above.